Avoiding chemo, especially when it doesn't cure any of us with CLL/SLL, has always made good sense. My readers know my mantra of protecting our bone marrow and immune defenses for the long term battles aheads again against infections and secondary cancers.
Now with the promise of the approval of all these new agents in sight, many CLL gurus (Kipps, Keating, Byrd and others) hail the twilight of chemo as frontline treatment. Today there are even more reasons to consider non-chemo " bridge therapies" to buy us time until the magic CLL slayers are approved or there is a trial open that accepts someone with our profile (not always easy).
Besides the short term misery of the side effects in the infusion center and for the weeks that follow, why put ourselves at increased risk for secondary cancers (especially other hematological malignancies), bone marrow damage with resulting cytopenias (low blood counts), infections, and maybe even an increased risk of auto-immune issues. If we can hang on for a year or two, we can get a much less toxic therapy from our drugstore, assuming we can find a way to pay the $10,000 or more a month cost, but that's another subject. See my friend, Dr. Jeff Sharman's blog at http://www.cll-nhl.com/2013/05/how-expensive-are-new-drugs.html?m=0 for a nice discussion of that issue.
The good news is that there are already several good non-chemo options available in trials or in the clinic, for use as single agents or in combinations.
Over the next few weeks I will offer up several for your consideration.
I will start with an old friend, one of the choices that is both on the market already and available in some interesting trials.
Lenalidomide (Revlimid), an immunomodulator, is approved for multiple myeloma (MM) and some special cases ofmyelodysplastic syndrome (MDS). In CLL, the NCCN recommends it as 1st line therapy for those over 70 or sicker younger patients with co-morbidities. That can help you get it off label and with a little bit of effort, have your insurance to help pay for it. At an estimated $425 for each daily 10 mg tablet at Walmart that translates to more than $150,000 per year, we all need some help.
That is one real unsung advantage to a clinical trial: the trial drugs are free.
And Revlimid is also available in several promising trials for CLL. There are two in particular that are very much alike that have me excited: NCT01766583 and NCT01732861 where it is combined with a very specific BTK inhibitor (CC-292 AKA AVI-292 or AVL-292) that is behind the leader of that pack in development, ibrutinib. More on that drug later. Both of these trials are for those with relapsed or refractory disease. Read the details. Call the co-ordinator. Become your own expert.
If you go on to http://clinicaltrials.gov/ct2/results?term=lenalidomide+CLL&Search=Search you'll find an impressive list of 75 different trials with lenalidomide for CLLers. Many of these are closed or not recruiting, many are in combo with chemo, and many have restrictive inclusion and exclusion criteria, but take a look and you may find something that fits your need to control the CLL.
Lenalidomide has several advantages. It is an oral medication. It may work better the longer you take it. It is an IMiD that modulates the immune system, and CLL is a disease of the immune system. It doesn't damage DNA or target rapidly dividing cells as does most chemo. It make sense that it might boost the efficacy of other therapies from vaccines to rituximab (AKA R+R), steroids and more.
And as I said, it's not "chemo.
Not that it a free ride. It can suppress blood counts especially neutrophils and platelets, increase infection risk, cause a nasty and potentially dangerous tumor flare and tumor lysis syndrome, make us very sleepy, increases the risk of dangerous blood clots, should never be taken if you could get pregnant (it is closely related to thalidomide that also works in CLL) and it has been associated with more secondary cancers.
Still, today, I definitely sees many circumstances where I would take it ahead of the gold standard, FCR or the new hottie, BR.
Do your homework and check it out.
More soon on other non-chemo options including new and old TKIs and the next generation of MaBs and others.
Also part two of the Wiestner interview from ASH and more details on my recent visit to OSU.
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Dr. Stephan Stilgenbauer on the Evolution of CLL to Richter’s Syndrome from ASH 2022